title: Human amniotic fluid stem cells suppress PBMC proliferation through IDO and IL-10-dependent pathways.
abstract: Human amniotic fluid stem cells (hAFSCs) can be readily isolated from human amniotic fluid and display multi-differentiation potential and immunomodulatory properties. The mechanism of hAFSCs immunoregulation has not been defined. Here, we explore the immunomodulatory effects of hAFSCs derived from human amniotic fluid and evaluate the role of IL-10 and the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) in mediating the immunosuppressive actions of hAFSCs. Flow cytometry showed that hAFSCs were positive for the mesenchymal stem cell markers CD29, CD44, CD105, HLA-ABC, and more than 84% of the hAFSCs were positive for SSEA-4, which is a typical marker of embryonic stem cell (ESCs), and negative for HLA-DR. The RT-PCR and immunostaining results revealed that the multipotent stem cells expressed OCT-4, Nanog, CD44, SOX2 and SSEA-1. In vitro differentiation assays demonstrated that hAFSCs underwent osteogenic differentiation. We examined the immunomodulatory function of hAFSCs using a co-culture system with phorbol 12-myristate 13-acetate (PMA) stimulated peripheral blood mononuclear cells (PBMCs). PBMC proliferation was suppressed by the hAFSCs in a dose-dependent manner. The inhibitory effect was caused by increased IL-10 and IDO induction after co-culture. Neutralizing the IL-10 activity or blocking the function of IDO partially abolished the immunosuppressive action of the hAFSCs. In conclusion, these results suggest that the hAFSCs possess immunomodulatory properties, and IL-10 and IDO are involved in immunosuppression by hAFSCs.
authors.forename: Chengfeng
authors.initials: C
authors.lastname: Luo
authors.forename: Wenwen
authors.initials: W
authors.lastname: Jia
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Fengli
authors.initials: F
authors.lastname: Chi
authors.forename: Yanqiong
authors.initials: Y
authors.lastname: Gu
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Yan
authors.forename: Gang
authors.initials: G
authors.lastname: Zou
authors.forename: Tao
authors.initials: T
authors.lastname: Duan
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040, People's Republic of China. qianzhou163@163.com.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D000653:Amniotic Fluid / Q000166:cytology; D015703:Antigens, CD / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D053595:Embryonic Stem Cells / Q000502:physiology*; D006801:Humans; D007155:Immunologic Factors / Q000378:metabolism; D007165:Immunosuppression Therapy; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000502:physiology*
chemical_list: D015703:Antigens, CD; C508609:IL10 protein, human; D007155:Immunologic Factors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D016753:Interleukin-10; D007371:Interferon-gamma